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Hormones = Chemicals secreted by a cell or group of cells into the blood, that act on distant target(s) and are effective at very low concentrations. Hormones play a major role in growth and development, metabolism, regulation of the internal environment (temperature, water balance, and ions), biological clock, contraction of cardiac and smooth muscle, some immune functions and reproduction. Hormones act on target cells three different ways: 1. By controlling the rates of enzymatic reactions (modulate activity, change amount of enzyme). 2. By controlling the transport of ion molecules across the membrane (open/close channels, modulate transporters). 3. By controlling gene expression and synthesis of proteins (³genomic effects´).
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Cellular mechanism of action = Biochemical response(s) initiated by hormone at target cell(s). Half-life = Amount of time required to reduce a hormone concentration in half Hormones must be transported via blood to distant targets.
Hormone Action Depends on Specific Receptors as Well as Hormone Properties.
Hormones only affect target cells with specific membrane proteins called receptors!!!!!!!!!
Distinction between nervous and endocrine system is no longer clear-cut
. 1. Exocrine glands y secrete products into ducts which empty into body cavities or body surface y sweat, oil, mucous, & digestive glands 2. Endocrine glands y secrete products (hormones) into bloodstream y pituitary, thyroid, parathyroid, adrenal, pineal y other organs secrete hormones as a 2nd function y hypothalamus, thymus, pancreas, ovaries, testes, kidneys, stomach, liver, small intestine, skin, heart & placenta Hormones Have Been Known Since Ancient Times ³Goiter was endemic high in the Andes due to lack of iodine in the diet. People living near the coast where they could eat seafood rich in iodine did not exhibit much goiter. In ancient China, low-iodine goiter was treated by drinking a powder of burnt seaweed dissolved in wine, an effective remedy because marine plants and animals contain substantial amounts of iodine´. Link between castration and endocrine structure/function 1. Link between testies and male sexuality: Castration of animals and men in both Eastern and Western culture was common practice decreased sex drive and male infertility. A. A. Berthold¶s experiments became a template for endocrine research: ³ In 1849 Berthold removed testies from roosters smaller combs & less aggressive. If testies were placed back into the bird normal behaviour and comb development. Since the re-implanted testies were not connected to nerves, the glands must be secreting something into the blood that affected the entire body´. The Classification of Hormones Hormones are categorized into three main chemical classes: y y y peptide/protein hormones (composed of amino acids) steroid hormones (derived from cholesterol) amino-acid hormones (modifications of single amino acids, either tryptophan or tyrosine)
Classic hormones: are hormones secreted by an endocrine gland or cell, may be a peptide, steroid, or amine in nature. Neurosecretory hormones: are hormones secreted by nerve cells and are either peptide or amines.
Most Hormones are Peptides or Proteins Peptide/protein hormones range from small peptides of only three amino acids to larger proteins and glycoproteins. Despite their size among hormones in this group they are usually called peptides for simplistic sake. You can remember which hormones fall into this category by exclusion: if a hormone is not a steroid hormone and not an amino acid derivative, then it must be a peptide or protein. Peptide Hormone Synthesis, Storage, and Release Synthesis and packaging of peptide hormones into membrane bound vesicles is similar of that to other proteins. 1 2 3 Initial peptide comes off ribosome is a large inactive protein known as a preprohormone (Preprohormones contain one or more copies of peptide hormones) As the inactive preprohormone moves through the endoplasmic reticulum and golgi complex, the signal sequence is removed, creating a smaller, still-inactive molecule called a prohormone. In the golgi complex, the prohormone is packaged into a secretory vesicles along with proteolytic enzymes that chop the prohormone into active hormone and other fragments. This process is called pot-translation modification The secretory vesicles containing peptides are stored in the cytoplasm of the endocrine cell until the cell receives a signal for secretion. The vesicles are transported out of the cell via calcium-dependent exocytosis
Post-translational Modification of Prohormone There are many possible scenarios for post-translational processing 1. Multiple copies of the hormone a) PreProTRH (thyrotropin-releasing hormone) has 6 copies of the 3-amino acid hormone TRH.
Prohormone¶s such as pro-opiomelanocortin, the prohormone for ATCH may contain several peptide sequences with biological activity
Cellular Mechanism of Action of Peptide Hormones A. Peptides are lipophobic (hate lipids), so they have membrane receptors. B. Signal transduction sets off cellular response. C. Can act on existing cell products, so have a quick response time.
Many peptides work through cAMP second messenger systems
Steroid Hormones are Derived from Cholesterol Steroid hormones have similar chemical structures because they are derived from cholesterol. Steroid hormones are made in only a few organs. Three types of steroid hormones are made in the adrenal cortex, the outer portion of the adrenal glands. The gonads produce sex steroids. In pregnant women, the placenta is also a source of steroid hormone.
Cellular Mechanism of Action of Steroid Hormones The best studied steroid hormones receptors are found within cells, either in the cytoplasm or nucleus. The ultimate destination of steroid receptor-hormone complexes is the nucleus, where the complex acts as transcription factor, binding to DNA and activating or depressing one or more genes. Activated genes create new mRNA that directs the synthesis of new proteins. Any hormone that alters gene activity is said to have a genomic effect on the target cell. When steroid hormones activate genes to direct the production of new proteins, there is usually a lag time between hormone receptor binding and the first measurable biological effects. This lag can be up to 90 min. Estrogens and aldosterone, have cell membrane receptors linked to signal transduction pathways, just as peptide hormones do. These receptors enable those steroid hormones to initiate rapid nongenomic responses in addition to slower genomic effects. 1. Intracellular receptors in cytoplasm or nucleus. 2. Hormone-receptor complex acts as a transcription factor directing synthesis of gene products. 3. Lag time of action due to synthesis of new proteins 4. Can have surface receptors/signal transduction (e.g., estrogen, aldosterone) with more rapid effects
Some Hormones are derived from Single Amino Acids A. Melatonin (tryptophan) B. Catacholamines (tyrosine): Behave like peptide hormones. C. Thyroid hormones (tyrosine): Synthesized more like peptide hormones, but behave like steroid hormones once released from the thyroid cell. The thyroid hormones are unique among hormones because iodine is a key part of each thyroid molecule. Like peptide hormones, thyroid hormones are made in advance and stored in an inactive form waiting release. Once converted to the active form, the thyroid hormones behave as if they are steroid hormones. Thyroid hormones are lipophilic so they diffuse freely across cell membranes and are carried bound to proteins in the blood. Only free (unbound) hormones diffuse across the target cell membrane to combine with a nuclear receptor. And like the steroid-receptor complex, the thyroid-receptor complex initiates transcription, translation and protein synthesis.
Negative Feedback Turns Off Hormone Reflexes
A. Negative feedback signal turns off response. 1. Ex. increased blood glucose levels reflex response decreased blood glucose turns off the reflex. B. Hormones act as negative feedback signals in complex reflexes C. Hormones usually act as negative feedback signals only when trophic hormones are involved
The Pituitary Gland is Actually Two Fused Glands
Neurohormones of the Posterior Pituitary
A. Stores and releases oxytocin and vasopressin (ant diuretic hormone). B. Peptides made in hypothalamus stored in secretory vesicles transported down an axon to posterior pituitary for release y y y Does not synthesize hormones Consists of axon terminals of hypothalamic neurons Neurons release two neurotransmitters that enter capillaries Oxytocin Two target tissues both involved in neuroendocrine reflexes y During delivery - baby¶s head stretches cervix hormone release enhances uterine muscle contraction and baby & placenta are delivered After delivery - suckling & hearing baby¶s cry stimulates milk ejection, hormone causes muscle contraction & milk ejection
Ant diuretic Hormone (ADH) Also known as vasopressin which functions include: 1 2 3 decrease urine production decrease sweating increase BP
Complex Endocrine Pathways Include Two or More Hormones
Hormones of the Anterior Pituitary A. Six hormones: prolactin, growth hormone (GH), the gonadotrophins (follicle-stimulated hormone, or FSH and leutinizing hormone, or LH), adrenocorticotrophic hormone (ATCH or corticotropin), thyroid stimulating hormone (TSH or thyrotropin) B. Of these, only prolactin is not trophic C. Feedback in hypothalamic-pituitary system 1. Concentration change of one hormone concentration change for other hormones in axis. 2. Long-loop negative feedback: Hormone from last integrating center affects secretion of trophic hormones from hypothalamus or pituitary 3. Short-loop negative feedback: Hormones of pituitary affect secretion of trophic hypothalamic hormone.
Human Growth Hormone Produced by somatotrophs Within target cells increases synthesis of insulin-like growth factors that act locally or enter bloodstream common target cells are liver, skeletal muscle, cartilage and bone increases cell growth & cell division by increasing their uptake of amino acids & synthesis of proteins stimulate lipolysis in adipose so fatty acids used for ATP retard use of glucose for ATP production so blood glucose levels remain high enough to supply brain Regulation of HGH Low blood sugar stimulates release of GHRH from hypothalamus ± anterior pituitary releases more hGH, more glycogen broken down into glucose by liver cells
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High blood sugar stimulates release of GHIH from hypothalamus ± less hGH from anterior pituitary, glycogen does not breakdown into glucose
Thyroid Stimulating Hormone (TSH) Hypothalamus regulates thyrotroph cells Thyrotroph cells produce TSH TSH stimulates the synthesis & secretion of T3 and T4 Metabolic rate stimulated
Follicle Stimulating Hormone (FSH) Releasing hormone from hypothalamus controls gonadotrophs Gonadotrophs release follicle stimulating hormone FSH functions ± ± ± initiates the formation of follicles within the ovary stimulates follicle cells to secrete estrogen stimulates sperm production in testes
Luteinizing Hormone (LH) Releasing hormones from hypothalamus stimulate gonadotrophs Gonadotrophs produce LH In females, LH stimulates ± ± ± ± secretion of estrogen ovulation of 2nd oocyte from ovary formation of corpus luteum secretion of progesterone
In males, stimulates interstitial cells to secrete testosterone
Prolactin (PRL) Hypothalamus regulates lactotroph cells Lactotrophs produce prolactin Under right conditions, prolactin causes milk production Suckling reduces levels of hypothalamic inhibition and prolactin levels rise along with milk production Nursing ceases & milk production slows
Adrenocorticotrophic Hormone Hypothalamus releasing hormones stimulate corticotrophs Corticotrophs secrete ACTH & MSH ACTH stimulates cells of the adrenal cortex that produce glucocorticoids
Melanocyte-Stimulating Hormone Secreted by corticotroph cells Releasing hormone from hypothalamus increases its release From the anterior pituitary Function not certain in humans (increase skin pigmentation in frogs )
A. Synergism: Combined action of hormones A+B > summed action of A alone + B alone B. Ex: epinephrine and glucagon Antagonism A. Antagonism: Hormone B diminishes the effect of hormone A. B. Ex: growth hormone or glucagon, both of which increases blood glucose, may be considered antagonistic to insulin
Permissiveness A. Permissiveness: Hormone A will not exert full effect without presence of hormone B B. Ex. throid hormone and growth hormone Antagonism: A. Antagonism: Hormone B diminishes the effect of hormone A B. Ex: growth hormone or glucagon, both of which increase blood glucose, may be considered antagonistic to insulin
The concept of antagonism is used several ways. In pharmacological antagonism, a drug is considered antagonistic if it binds to and inactivates a receptor for another drug by acting as either a competitive or allosteric competitor. For example, mifepristone, better known as RU 486, is an artificial steroid that binds to the progesterone receptor and prevents endogenous progesterone from binding. In physiologic antagonism, two molecules need only have opposing physiological effects to be considered antagonists. Thus, glucagon and insulin are antagonistic because of their opposing effects on blood glucose. Growth factors fall into two sets of antagonistic molecules, those that stimulate growth and those that inhibit it. The opposing effects of growth factors may occur at the levels of the signal transduction pathway, with one factor increasing cAMP levels while the antagonistic factor decreases it.